Surgical Access Combined With Systematically Administered Antibiotics in the Treatment of Peri-implantitis

July 17, 2024 updated by: Jamil awad shibli, University of Guarulhos

Clinical and Microbiological Effects of Surgical Access Combined With Systematically Administered Antibiotics in the Treatment of Peri-implantitis: 1-year Randomized Double-blinded Controlled Clinical Trial

This randomized clinical trial evaluates the clinical and microbiological (microbial complexes and changes in the diversity of the submucosal biofilm) effects of MTZ+AMX as adjuncts to anti-infectious surgical treatment plus Er: YAG in the treatment of peri-implantitis.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Peri-implantitis is a pathological condition characterized by inflammation of peri-implant connective tissues and progressive peri-implant bone. Recently, the therapeutic protocol using non-surgical debridement associated with the combination of systemic metronidazole (MTZ) and amoxicillin (AMX) has not been shown to be effective in controlling the disease. These unfavorable results may have occurred due to the limitation in the change of the submucosal microbiological profile due to mechanical difficulties in the decontamination of the implant threads. Therefore, this randomized clinical trial (RCT) aimed to evaluate the clinical and microbiological (microbial complexes and changes in the diversity of the submucosal biofilm) effects of MTZ+AMX as adjuncts to anti-infectious surgical treatment plus Er:YAG in the treatment of peri-implantitis. Ninety-four subjects with untreated peri-implantitis are being included and will be randomly assigned to receive (i) open flap debridement plus Er:YAG irradiation alone (control), or (ii) with adjunctive systemically administered MTZ (400 mg) + AMX (500 mg) thrice a day (TID) for 14 days (test). Subjects will be monitored up to 12 months post-treatment. Submucosal biofilm samples from the deepest site of each implant with peri-implantitis will be collected in duplicate per patient: at baseline and at 3, 6 and 12 months post-therapy and analyzed by checkerboard DNA-DNA hybridization for 40 bacterial species, and at baseline, 3 and 12 months post-treatment for 16S rRNA sequencing (Ion Torrent PGM System). The primary outcome variable of this trial will be the difference between treatment groups for the change in CAL from baseline to 12 months. The significance of differences in each group (over the course of the study) will be sought using the Student's-t test; and among groups (at each time point) using either ANOVA /ANCOVA or Kruskal Wallis tests and post-hoc analyses, depending on normality of the data. Fisher's exact test will be used to compare differences in the frequency of gender. Statistical significance will be set at 5%.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
89

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Jamil A Shibli, Professor
  • Phone Number: +55 11 2464-1726
  • Email: jshibli@ung.br

Study Contact Backup

  • Name: Magda Feres, Professor
  • Phone Number: +55 11 2464-1726
  • Email: mferes@ung.br

Study Locations

  • Brazil
    • São Paulo
      • Guarulhos, São Paulo, Brazil, 07023-070
        • University of Guarulhos

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18-70 years of age;
  • in general good health,
  • at least one dental implant in function for at least one year with untreated peri-implantitis defined as: presence of bleeding and/or suppuration on gentle probing, probing depths (PD) ≥ 6mm, and bone levels ≥3mm apical of the most coronal portion of the intraosseous part of the implant.

Exclusion Criteria:

  • subjects with ≥6 sites with PD ≥5mm;
  • individuals that received periodontal treatment within three months prior to entering the study;
  • inability to perform proper supramucosal and supragingival plaque control (e.g., due to improper restoration design or lack of skills);
  • poorly adapted implant-supported restoration;
  • diabetes;
  • pregnancy;
  • nursing;
  • history of allergies to metronidazole and/or amoxicillin, or any other ingredient of oral care products;
  • alcohol or drug abuse;
  • any systemic diseases that could affect post-operative healing or that required antibiotic premedication for routine dental therapy;
  • long-term use of mouthrinses;
  • anti-inflammatory medications;
  • any other drug that could interfere with the study outcomes within three months prior to entering the study;
  • use of antibiotics within six months prior to entering the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Control
Open flap debridement + Er: YAG irradiation alone + systemic placebo of metronidazole and amoxicillin thrice a day (TID) for 14 days
Procedure: Open flap debridement
After local anesthesia (2% lidocaine with1:100,000 epinephrine), intrasulcular incisions will be performed to create a horizontal flap extending beyond the adjacent teeth and/or implants. Buccal and lingual full-thickness flaps will be dissected, and granulation tissue will be removed to expose the implant threads and bone defect. The flap will be repositioned in its original position and stabilized with interrupted sutures, which will be removed after 10 days.
Other Names:
  • OFD
Other: Er: YAG irradiation
An Er:YAG laser (Lite Touch, Light Instruments, Israel) will be used, with an irradiation energy of 20 mJ, frequency of 20 Hz, output power of 0.4 W, and an energy density of 2.76 J/cm2. An 8 mm long sapphire tip will be used in the respective handpiece and not in contact with the titanium surface, with concomitant water spray irrigation, under air 6 and water spray 6, the irradiation angle will be 90 degrees, at a focal distance of 2 mm, with spot size diameter of 1.3 mm
Drug: Placebos
Amoxicillin and metronidazole placebos thrice a day for 14 days in the healing phase (beginning after open flap debridement).
Experimental: Test
Open flap debridement + Er: YAG irradiation alone + systemic metronidazole (400mg) and amoxicillin (500mg) thrice a day (TID) for 14 days
Procedure: Open flap debridement
After local anesthesia (2% lidocaine with1:100,000 epinephrine), intrasulcular incisions will be performed to create a horizontal flap extending beyond the adjacent teeth and/or implants. Buccal and lingual full-thickness flaps will be dissected, and granulation tissue will be removed to expose the implant threads and bone defect. The flap will be repositioned in its original position and stabilized with interrupted sutures, which will be removed after 10 days.
Other Names:
  • OFD
Other: Er: YAG irradiation
An Er:YAG laser (Lite Touch, Light Instruments, Israel) will be used, with an irradiation energy of 20 mJ, frequency of 20 Hz, output power of 0.4 W, and an energy density of 2.76 J/cm2. An 8 mm long sapphire tip will be used in the respective handpiece and not in contact with the titanium surface, with concomitant water spray irrigation, under air 6 and water spray 6, the irradiation angle will be 90 degrees, at a focal distance of 2 mm, with spot size diameter of 1.3 mm
Drug: Metronidazole
Metronidazole 400 mg thrice a day for 14 days in the active phase of the periodontal treatment (beginning after open flap debridement).
Other Names:
  • MTZ
Drug: Amoxicillin
Amoxicillin 500 mg thrice a day for 14 days in the active phase of the periodontal treatment (beginning after open flap debridement).
Other Names:
  • AMX

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Difference between treatment groups for the change in the clinical attachment level (CAL).
Time Frame: 12 months.
12 months.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Percentage of sites with bleeding on probing.
Time Frame: Baseline, 3, 6 and 12 months.
Baseline, 3, 6 and 12 months.
Occurrence of headache obtained through a questionnaire of adverse effects.
Time Frame: 14 days after taking antibiotic.
14 days after taking antibiotic.
Occurrence of vomiting obtained through a questionnaire of adverse effects.
Time Frame: 14 days after taking antibiotic.
14 days after taking antibiotic.
Occurrence of diarrhea obtained through a questionnaire of adverse effects.
Time Frame: 14 days after taking antibiotic.
14 days after taking antibiotic.
Occurrence of metallic taste obtained through a questionnaire of adverse effects.
Time Frame: 14 days after taking antibiotic.
14 days after taking antibiotic.
Occurrence of nausea obtained through a questionnaire of adverse effects.
Time Frame: 14 days after taking antibiotic.
14 days after taking antibiotic.
Occurrence of irritability obtained through a questionnaire of adverse effects.
Time Frame: 14 days after taking antibiotic.
14 days after taking antibiotic.
Proportions of periodontal pathogenic bacterial species.
Time Frame: Baseline, 3, 6 and 12 months.
Baseline, 3, 6 and 12 months.
Counts of periodontal pathogenic bacterial species.
Time Frame: Baseline, 3, 6 and 12 months.
Baseline, 3, 6 and 12 months.
Percentage of patients (and implants) reaching the following clinical endpoint for treatment: PD< 5mm, absence of BOP and no further bone loss.
Time Frame: 12 months.
12 months.
Mean plaque index.
Time Frame: Baseline, 3, 6 and 12 months.
Baseline, 3, 6 and 12 months.
Mean gingival index.
Time Frame: Baseline, 3, 6 and 12 months.
Baseline, 3, 6 and 12 months.
Percentage of sites with suppuration.
Time Frame: Baseline, 3, 6 and 12 months.
Baseline, 3, 6 and 12 months.
Probing depth.
Time Frame: Baseline, 3, 6 and 12 months.
Baseline, 3, 6 and 12 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Guarulhos

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
ITI Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jamil A Shibli, Professor, University of Guarulhos

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 16, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 16, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 29, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 5, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 18, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 40892620.9.0000.5506
  • 1454_2019 (Other Identifier: ITI Research Grant)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings